Herpes simplex virus type 1 ICP0 protein mediates activation of adeno-associated virus type 2 rep gene expression from a latent integrated form

J Virol. 2004 Oct;78(20):10977-86. doi: 10.1128/JVI.78.20.10977-10986.2004.


Adeno-associated virus type 2 (AAV-2) is a human parvovirus that requires the presence of a helper virus, such as the herpes simplex virus type 1 (HSV-1) to accomplish a complete productive cycle. In the absence of helper virus, AAV-2 can establish a latent infection that is characterized by the absence of expression of viral genes. So far, four HSV-1 early genes, UL5/8/52 (helicase primase complex) and UL29 (single-stranded DNA-binding protein), were defined as sufficient for AAV replication when cells were transfected with a plasmid carrying the wild-type AAV-2 genome. However, none of these viral products was shown to behave as a transcriptional factor able to activate AAV gene expression. Our study provides the first evidence that the immediate-early HSV-1 protein ICP0 can promote rep gene expression in cells latently infected with wild-type AAV-2. This ICP0-mediated effect occurs at the transcriptional level and involves the ubiquitin-proteasome pathway. Furthermore, using deletion mutants, we demonstrate that the localization of ICP0 to ND10 and their disruption is not required for the activation of the rep promoter, whereas binding of ICP0 to the ubiquitin-specific protease HAUSP makes a significant contribution to this effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dependovirus / genetics
  • Dependovirus / physiology*
  • Endopeptidases / metabolism
  • Gene Expression Regulation, Viral*
  • HeLa Cells
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / metabolism
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Transcription, Genetic
  • Ubiquitin Thiolesterase
  • Ubiquitin-Protein Ligases
  • Ubiquitin-Specific Peptidase 7
  • Vero Cells
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Virus Activation*
  • Virus Latency
  • Virus Replication


  • DNA-Binding Proteins
  • Immediate-Early Proteins
  • Viral Proteins
  • rep proteins, Adeno-associated virus 2
  • Ubiquitin-Protein Ligases
  • Vmw110 protein, Human herpesvirus 1
  • Endopeptidases
  • USP7 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Peptidase 7